Febrile neutropenia

Russell E. Lewis
Associate Professor of Infectious Diseases
Department of Molecular Medicine
University of Padua

{{< fa solid envelope size=1x >}} russelledward.lewis@unipd.it
{{< fa brands github size=1x >}} https://github.com/Russlewisbo

Objectives

• What are the most common infections associated with short versus prolonged neutropenia?

• How does the presentation of skin, mucocutaneous lesions, abdominal pain or pneumonia change the infection differential diagnosis?

• What are common empiric antimicrobial regimens used

Normal hematopoiesis

Chemotherapy-associated neutropenia

• Virtually all antineoplastic impair proliferation of normal hematopoietic progenitor cells

  • Obliteration of the mitotic pool

  • Depletion of the marrow reserve

• Antineoplastic drugs, glucocorticoids and irradiation also interfere with the function of non-proliferating granulocytes, resulting in:

  • Decreased chemotaxis

  • Diminished phagocytic capacity

  • Defective intracellular killing

Chemotherapy-associated neutropenia

• Glucocorticoids seem to enhance granulocytopoiesis and mobilize the marginal and marrow pool reserve, but…

  • reduce accumulation of granulocytes at site of infection (reduced adherence)

  • diminished chemotactic activity

  • decreased phagocytosis and intracellular killing

Quantitative relationship of neutropenia with infection risk

Clinical signs if infection are muted in neutropenic patients

% of patients who have a neutrophil count/mm³ of:

Model of mucosal barrier injury

Dysbiosis

Which bacterial pathogens translocate?

Severity of mucositis

WHO toxicity scale

Sequence of infection in febrile neutropenia